The radio sensitising effect of gemcitabine and the influence of the rescue agent amifostine in vitro
The radio sensitising effect of gemcitabine and the influence of the rescue agent amifostine in vitro
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DOI：
10.1016/s0959-8049(03)00002-9
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发表时间：
2003-04-01
影响因子：
8.4
通讯作者：
Vermorken, JB
中科院分区：
文献类型：
--
作者：
Pauwels, B;Korst, AEC;Vermorken, JB
在这项研究中，不同浓度的吉西他滨和吉西他滨/放疗与救援剂氨磷汀的组合的放射增敏作用在不同的人肿瘤细胞系中进行了研究。在辐射（0 -8戈伊）之前，用吉西他滨（0 -8 nM）处理细胞24 μ l。放射前30 min加入氨磷汀（ami）和碱性磷酸酶（AP）。放射处理后7或8天，通过磺酰罗丹明B（SR B）试验测定细胞存活率。对于ECV 304细胞，用1-6 nM吉西他滨处理后，剂量增强因子（DEF）从1.39变化到2.98。FaDu、H292、A549和CAL-27似乎不太敏感，DEF范围为1.02至2.67。这些细胞对单药吉西他滨的细胞毒性作用也不太敏感。氨磷汀与AP联合吉西他滨/放疗明显显示出保护作用。在H292细胞中，经吉西他滨和放疗处理后，氨磷汀的保护因子（PF）在1.64至1.86之间变化。在ECV 304细胞中，PF在2.20至2.29之间变化。总之，在所有细胞系中均观察到吉西他滨具有明显的浓度和细胞系依赖性放射增敏作用。氨磷汀与AP对吉西他滨的放射增敏作用有保护作用。如果体内保护作用确实选择性地发生在正常组织中，则氨磷汀可以预防或强烈地最小化由吉西他滨和放射治疗的组合的放射增敏作用引起的增加的毒性，而不影响抗肿瘤作用。(C)2003爱思唯尔科技有限公司版权所有。
In this study, the radio sensitising effect of different concentrations of gemcitabine and the combination of gemcitabine/radiotherapy with the rescue agent amifostine was investigated in different human tumour cell lines. The cells were treated with gemcitabine (0-8 nM) for 24 It prior to radiation (0-8 Gy). Amifostine (ami) and alkaline phosphatase (AP) were added 30 min before radiation. Cell survival was determined 7 or 8 days after radiation treatment by the sulforhodamine B (SRB) test. For ECV304 cells, the dose enhancement factor (DEF) varied from 1.39 to 2.98 after treatment with 1-6 nM gemcitabine. FaDu, H292, A549 and CAL-27 seemed to be less sensitive, with DEFs ranging from 1.02 to 2.67. These cells were also less sensitive to the cytotoxic effects of single-agent gemcitabine. Amifostine with AP clearly showed a protective effect in combination with gemcitabine/radiotherapy. In H292 cells, the protection factor (PF) of amifostine after treatment with gemcitabine and radiotherapy varied from 1.64 to 1.86. In ECV304 cells, the PF varied from 2.20 to 2.29. In conclusion, a clear concentration- and cell line-dependent radiosensitising effect of gemcitabine was observed in all cell lines. Amifostine with AP showed protection against the radiosensitising effect of gemcitabine. If the protection in vivo indeed occurs selectively in normal tissues, then amifostine could prevent or strongly minimise the increased toxicity resulting from the radiosensitising effect of the combination of gemcitabine and radiotherapy, Without influencing the antitumour effect. (C) 2003 Elsevier Science Ltd. All rights reserved.